Impurities Lab Report

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Tolfenamic Acid There are three impurities of note in relation to tolfenamic acid. A sample must be within the limits for these named impurities as well as any other impurities. The three named impurities are 2-chlorobenzoic acid, 3-chloro-2-methylaniline and 3-chloro-4-methyl-9-oxo-9, 10-dihydroacridine. 2-chlorobenzoic acid and 3-chloro-2-methylaniline are listed as impurities because they are starting materials in the synthesis of tolfenamic acid which did not react. Liquid chromatography is employed to assess the quantities of each impurity and a reference sample containing a known concentration of both impurities is used as comparison. The area of the peak in the chromatogram which corresponds to 2-chlorobenzoic acid must not be more than…show more content…
The European Pharmacopoeia monograph for mefenamic acid states that there are five main impurities to consider. Specified impurities include 2, 3-dimethylalanine (Impurity A), 2-chlorobenzoic acid (impurity C) and benzoic acid (impurity D). Other unspecified impurities include N-(2, 3-dimethylphenyl)-2-[(2, 3-dimethylphenyl)amino]benzamide (impurity B) and 2,3-dimethyl-N-phenylaniline (impurity E). 2-chlorobenzoic acid and 2,3-dimethylaniline are starting materials in the synthesis of mefenamic acid which failed to react, which would explain their presence as impurities. Liquid chromatography is used to test for the presence and concentration of impurities A, C and D. the monograph provides details on how to identify these compounds in a chromatogram based on their retention times in relation to mefenamic acid. Impurities C and D should not be present in a sample above the centration of 0.1 percent while impurity A has a limit of 100ppm. Impurity B results from reaction between an already formed mefenamic acid molecule and a molecule of 2, 3-dimethylalanine (impurity A). The amine group of impurity A attacks the carboxylic group of the mefenamic acid, which results in loss of water and formation of a new amide bond which forms Impurity B. Impurity E is most likely a result of benzyne formation from 2-chlorobenzoic…show more content…
It is typically seen as a pale yellow powder, which is practically insoluble in water, freely soluble in acetone and soluble in methanol and ethanol. It has been used in inflammatory and musculoskeletal disorders with usual oral doses of about 250 mg three or four times daily. It has also been used topically as a 3% ointment or 2.5% gel. Specified impurities of niflumic acid include 2-chloropyridine-3-carboxylic acid (Impurity A), 2-hydroxy-N-[3-(trifluoromethyl)phenyl]pyridine-3-carboxamide (Impurity B) and 3-(trifluoromethyl)aniline (Impurity C). Impurity A is analysed via liquid chromatography and has a limit of 0.1 percent. Impurity B is also analysed by liquid chromatography but has a limit of 0.4 percent. Impurity A is unreacted starting material which was not removed during purification. Impurity B is the product of a reaction between the carboxylic group of 2-hydroxypyridine-3-carboxylic acid (most likely an impurity of 2-chloropyridine-3-carboxylic acid), and the amine group of 3-(trifluoromethyl)aniline resulting in formation of an amide bond with loss of water. Impurity C, similar to impurity A, is unreacted starting material. However its presence and concentration is determined via thin layer chromatography. A test solution and a reference solution are prepared and on comparison,

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